Preparation of n, n&#39;-methylene bis hydantoins



Patented Mar. 25, 1947 UNITED STATE S PATENT OFFICE A PREPARATION OF N,N'-METHYLENE BIS HYDANTOINS No Drawing. Application February 7, 1945, Serial No. 576,705

7 Claims. 1

This application is a continuation-in-part of my copending application Serial No. 484,638, filed April 26, 1943.

This invention relates to the preparation of monomeric N,N methylene bis-hydantoins and substituted hydantoins and to certain new chemical compounds thereby produced. More particularly, it is directed to the preparation of N,N' methylene bis-hydantoins, including bis-hydantoins containing One or more alkyl substituents in the -position and in which the total number of carbon atoms in the substituent roups does not exceed 5, by a process wherein a hydantoin is reacted with formaldehyde or paraformaldehyde in an aqueous medium comprising concentrated hydrochloric acid, there being present in said reaction medium a salt of zinc or cadmium which serves to catalyze the reaction.

The invention also relates to certain new chemical compounds which can be readily prepared by this process, including N,N methylene bis 5-alkyl hydantoins in which at least one substituent group contains more than one carbon atom and the total number of carbon atoms in the substituent group does not exceed 5.

My invention is particularly useful in the case of alkyl substituted hydantoins containing a substituent in the 5-position having more than one carbon atom. These hydantoins tend to give liquid products on reaction with formaldehyde in the absence of zinc or cadmium chlorides.

Hydantoin, a chemical compound having the formula:

is also available in the form of its fi-monoalkyl and 5,5-dialkyl derivatives, all of said hydantoins being represented generally by the formula:

wherein R1 and R2 represent hydrogen or alkyl,

and may be the same or different radicals.

The principal object of this invention is the development of. a new. and improved process for the preparation of N,N'-methylene bis-hydantoins, including N,N-methyl bis-hydantoins containing one or two alkyl substituents in the 5-position of the hydantoin groups, the total number of carbon atoms in the substituents not exceeding 5, by reacting the hydantoin or substituted hydantoin with formaldehyde (or source of formaldehyde, for example, paraformaldehyde) in an aqueous reaction medium strongly acidified with hydrogen chloride and containing either zinc chloride or cadmium chloride as the reaction catalyst. The zinc or cadmium chloride may be added as such or these salts may be formed by the addition of a soluble zinc saltor of a soluble cadmium salt-to the strongly acidic reaction medium. The reaction occurring may be represented generally by the following equation:

wherein R1 and R2 represent hydrogen or the same or different radicals, the total number of carbon atoms in the alkyl radicals not exceeding 5. The alkyl radicals may be straight-chain or branched-chain, up to and including 5 carbon atoms. Both R1 and R2 may be hydrogen or R1 or R2 may be hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert. butyl, or amyl, and if R1 and R2 both represent alkyl radicals they may be methyl, methyl; methyl,. ethyl; methyl, propyl; methyl, butyl; ethyl, ethyl; or ethyl, propyl (including the isomeric propyl and butyl alkyls) By the use of zinc chloride or cadmium chloride as the catalyst in the aqueous solution strongly acidified with hydrogen chloride it is possible to utilize temperatures in the range of 30 C. to C. In place of formaldehyde any material equivalent to formaldehyde in the acid solution, such as paraformaldehyde or trioxane may be employed.

It is generally preferred to have the hydantoin and the formaldehyde present in the reaction mixture in the approximate proportion of one mole formaldehyde for each two moles of hydantoin. If, in preparing the reaction mixture, it is inexpedient to have the hydantoin and formaldehyde in the exact proportions-referred to, it is then preferred that the hydantoin, rather than the formaldehyde, be present in excess. Excess 2Dimethyl hydantoin 3 hydantoin, i. e., in excess of two moles per mole of formaldehyde, does not react and hence must be recovered or wasted. Excess formaldehyde, on

the other hand, favors formation of resinous byproducts.

Although there are individual differences between the various alkyl hydantoins, in general, the reaction mixture, at the initiation of the reaction,- must contain a quantity of water within the limits 15 to 35% by weight. The mixture must also contain hydrogen chloride to the extent of at least one part hydrogen chloride to four parts water by weight. The quantity of zinc reaction mixture, thereby permitting adequate chloride or cadmium chloride present may range from approximately 0.5% to 50% by weight of the .thefhydantoins containing a lesser number of carbpn atoms in thesubstituent groups. Concentration ranges of hydrogen chloride in the reaction mixture for best yields of methylene bis derivatives .are listed below for three substituted hydantoins Per cent hydrogen chloride in reaction mixture Methyl ethyl hydantoin 9-14 'Methylisobutyl hydantoin 16-19 "The ratio of hydrogen chloride to water required respectively for the above examples should be equivalent to hydrochloric acid of the following concentrations: -40% for dimethyl hydantoin,

2540% for methyl ethyl hydantoin, and 40% for methyl isobutyl hydantoin. In the case of methyl isobutyl hydantoim-in order to obtain the best yields, the reaction mixture should besaturated .with hydrogen chloride andshould contain at least about 8% of the zinc chloride catalyst.

Generally the reaction when the temperature is 50 C. to 70 C. or higher is complete after about 6 -.hours. While the reaction generally proceeds morerapidly-at temperatures close to 100 C., the netyield ofproduct is somewhat less at these temperatures than at relatively lower temperatures.

Both zinc chloride and cadmium chloride are suitableascatalysts, the amount giving most sati'sfactory results being generally in the neighborhood of 50 grams per mole of formaldehyde reacted. The zinc. or cadmium may be introduced ing'up to 5 carbon atoms, but as long as the alkyl substituent or substituents are lower alkyl groups 'asfhereindefined, I have obtained satisfactory "yields of product regardless of the substituent within reaction periods of reasonable duration 'utilizingmy acidic reaction medium and zinc or cadmium chlorides as the catalyst.

The reagent concentrated hydrochloric acid of density 1.19, containing 37% of hydrogen chloride, will give very satisfactory results, as will acid-"prepared by saturation with hydrogen chloride gas (equivalent to approximately 43% I-ICl concentration) Ingeneral, glass-lined or stoneware equipment dilution of the concentrated acid reaction medium in washing and recovering the product. The filter used to remove the product from the reaction medium must be resistant to hydrochloric acid; and the resulting product is dried in'a drying'oven or by means of a heated drum drier. As ordinary crude hydantoin or monoalkyl'or dialkyl derivatives thereof may contain traces of cyanides, suitable precautions should be taken to avoid exposure to any hydrogen cyanide fumes resulting whenacid is added to the hydantoin.

The 'N,N' methylene bis-hydantoins are solids of high stability and possess the property of forming salts with bases and metals. They dissolve in alkaline solutions and are reprecipitated by acids. They are also soluble in methanol, ethanol, and glacial acetic acid. They are valuable as compounds possessing both alkaline and acidic; properties to a certain degree and, when chlorinated, they yield valuable active chlorine compounds suitable for various uses in industrial and home processes.

As examples of my new and improved method for the manufacture of N,N' methylene bis-hydantoins, which hydantoins may contain one or more lower alkyl substituents in the 5-position,

the following may be given.

EXAMPLE 1 MN methylene bis dimethyl hydantoin 5,5-dimethyl hydantoin in the amount of "63.2 gram moles was reacted with 37% formaldehyde solution equivalent in amount to 31.6 gram moles of formaldehyde. Zinc chloride in the amount of 720 grams was utilized as a catalyst. The reaction medium consisted of 4.5liters of concen- 'trated hydrochloric acid (density 1.19).

The concentrated hydrochloric acid was placed in :a ten-gallon'stoneware crock fitted with a glass heating coil and double-bladed stirrer. The crock was then immersed in a hot water bath, and zinc chloride dissolved in the acid. In place of zinc chloride any other soluble zinc salt could be used, as this would react with the hydrochloric acid to form zinc chloride in the reaction medium. Also, the zinc salt could be replaced by a cadmium salt, thus introducing cadmium chloride as catalyst.

The dimethyl hydantoin was then added, with agitation, to the reaction medium and the crock .and its contents heated to 70C. The aqueous formaldehyde solution was next added over a periodof '15 minutes, heating being continued during this period. The steam supply to the heating coil was then shut off since the reaction at this point became exothermic in character and a rise of temperature to, C. or to C. is possible. When the temperature fell below this range the steam supp-1y was turned on again from time to time, to an extent sufficient to insure a temperature in the neighborhood of 100 C.

After one hour and 40 minutes the reaction was substantially complete and from 2 to '4 gallons of water was added to break up thesoli'dified amnesia product. :The product was then filtered affirm; the reaction medium and washed repeatedly in warm water. It was purified by dissolving the crude product in caustic solution and then filtering, the product being reprecipitated from this solution by neutralization with hydrochloric acid. Finally the purified product was filtered off, washed free of acid, and dried at a temperature of 120 C.

The yield was 6856 grams of N,N' methylene This is a yield of 81% on the basis of the 5,5-dimethyl hydantoin used up in the reaction If necessary in order to cool the slurry during acid in an amount equivalent to 2 to 3 liters may be added sometime during the course of thereaction. In this way excessive thickening of the reaction mixture can be avoided.

- EXAMPLE 2 N ;N" methylene bis 5-methyl, 5-ethyl hydantoin 5- methyl, 5-ethyl hydantoin inthe amount of 2891 grams (19.2 moles) was reacted with 761 grams (9.4 moles CHzO) of 37% formaldehyde solution in a reaction medium comprising 470 grams of zinc chloride catalyst and 940 cubic centimeters of concentrated hydrochloric acid. Additional hydrogen chloride gas was added to the reaction mixture in amount suflicient to saturate the mixture. ...Th,e hydrochloric acid-containing reaction medium was placed in a round-bottomed flask, of 12 liters capacity fitted with a stirrer, gas inlet and thermometer. The zinc chloride catalyst was dissolved in the hydrochloric acid and the 5- methyl, 5-ethyl hydantoin added thereto. Onehalf of the formaldehyde necessary was then introduced and the slurry saturated by the addition of hydrogen chloride gas.

During the first part of the reaction the temperature of the reaction mixture was maintained at'60' to 65 C., the contents of the flask bein subjected to agitation. After minutes the remaining amount of formaldehyde was added and the reaction mixture again saturated with hydrogen chloride gas. After four hours the temperature of the reaction mixture was elevated to 80 to 85 C. and maintained approximately in this ran e for two more hours. At the end of this time 6 liters of cold water was added to the reaction medium which was stirred until the'solidifled product had been thoroughly dispersed therein. The product was then filtered off, washed repeatedly in warm water, and dried.

The N,N' methylene bis 5-methyl, 5-ethyl hy-- dantoin resulting was recovered in the amount of 2270 grams, representing a yield of 82% of the theoretical based on the amount of formaldehyde utilized.

- EXAMPLE 3 N,N' methylene bis 5-methyl, 5-z'sobutyl hydantoin In preparing this product 1.07 moles grams) of 95% paraformaldehyde was utilized. This was reacted with 5-methyl, fi-isobutyl hydantoin .ina reaction medium comprising 200 '10 bis 5,5-dimethyl hydantoin having the following 6. cubic centimeters "of concentrated hydrochloric acid and containing. 200 grams orzinc chloride as catalyst; The amountof fi methyl, 5-isobutyl hydantoin utilized was equivalent to substantially 2 moles (340 grams) f'LThBYIZiI'iCichloridei was first dissolved in the concentrated acidand the 5-methy1, 5-isobutyl hydantoin added. The slurry was then saturated with hydrogen chloride gas and the paraformaldehyde added.

The temperature was maintained approxi- .niately in the range 30 to 35 C. and the reaction mixture allowed to stand for approximately 5 days. At the end of that time the reaction mixture was diluted by the addition of 3 liters of water, and then agitated to break up the caked product, the solid product was filtered off, washed twice in two liters of boiling water,

an oven at 110 C. 20

of N,N '-meth lene bis 5-meth l, 5-isobut l h the reaction period, cold water or hydrochloricy y y and dried in The recovery was approximately 237.5 grams dantoin, constituting a yield of approximately 67.5% based on the amount of the dialkyl hydantoin reacted.

The reaction medium consisted of 2.5 grams concentrated hydrochloric acid (37%) containing as catalyst approximately 0.4 gram of zinc chloride.

A The Zinc. chloride was first dissolved inthe acidic reaction. medium, and the S-mono-n-propyl hydantoin and formaldehyde solution were- EXAMPLE 5 N,N' methylene Dis-S-methyl, 5-isopropz/l hydantoin In preparing this product 400 grams of zinc chloride were dissolved in 476 grams concentrated hydrochloric acid (37%). To this solution was added 680 grams of 5,5-methyl, isopropyl hydantoin. When this had been stirred into the mixture 70 grams of paraformaldehyde was added, and the resultant mixture was saturated with hydrogen chloride gas. The reaction mixture was then allowed to stand for approximately 20 days, after which it was poured into 6 liters of cold water with agitation, and allowed to stand until the product had crystallized, The product was then filtered from the solution and washed with boiling'water. A yield of 463 grams N,N' methylene bis 5-methyl. 5-isopropyl hydantoin was obtained.

My new chemical compounds may be generically represented by the formula:

wherein X and Y represent the same or different radicals selectedfrom-the group which consists 7" of hydrogen andtlower alkyl radicalsatleastlone of which contains at leastltwo carbon atoms;

mam

prises reacting a hydantoin' having the formula The observedp ysical properties of "the N,Nv' g El methylene bis derivatives;of;;5-dimethylrhydanl toin, 5-methyl, 5-ethyl hydantoin, fi -methyl, 5 5-isobutyl hydantoin, and 5V-ni-propyl hydantoin are givenin'thesfollowing table: 1 I;

N,N'V methylene bisxderivativesiof 5-metl1yl: fi methyl I 5,5-d1methyl 59th li-n-propyl. e -i yl. o-isobutyl hydantom hydantoin hydantoin hydanmm Molecular weight '168 296 352 296. Color colorless.-. 'co10r1ess colorless; colorless. Meltingpoint et-296C.-- zss-zsc on- 213-22o'o. 205-2070. So1ubilityinwater t I (a)Vat25C ,o.5% 0.08% p (b) at 100 0 .*2;o%- 0.69 Solubility in tetrachlo- 0;04%.. 0.09%.-

rethane (25 0.).

a r l The N,N methylenebis-fi-mcthyl fi-lsobutylhydantoin is apparently a mixture point.

Various modifications of the process 'as described above with reference to certain preferred embodiments thereof will occur to those skilled in the art. It is, therefore, understood. that various changesmay bemade in the amounts, temperatures and procedures given herein as illustrative of those preferred embodiments without departing'from' the spirit or scope of myinvention.

Iclaim:

'1. The method ofpreparing an N,N' methylene bis hydant'oinhavingithe formula HN--C=O O=CNH wherei'nRr and R2 represent the same or different radicals selected from. the group which consists of hydrogen and alkyl radicals which comprises reacting a hydantoin having the formula R1 and R2 representing the above-identified radicals, and in which the total number of carbon atoms in R1 and R2 does not exceed 5, withformaldehyde in an aqueous reaction mixture containing, at the initiation of the reaction, the hydantoin and formaldehyde in the approximate proportion of one mole of formaldehyde for each two moles of the hydantoin, water in an amount between 15% and by weightof the reaction mixture, at least one part hydrogen chloride for each four parts of Water, and a metallic chloride taken from the group consisting of Zinc chloride and cadmium chloride. n

2. The method of preparing an N,N-' methylene bis hydantoin having the formula 1 wherein R1 and R2 represent the same or different radicals selected, from thegroupwhich con.- sists of hydrogen and alkyl radicals which comof stereo-isomers, from which it is impossible to obtain aproductof sharp melting 7 R1 and R2 representing the above-identified-radlcals, and in which the total number of carbon atoms in R1 and R2 does not exceed 5, with formaldehyde in an aqueous reaction mixture containing, at the initiation of the reaction, the hydantoin and formaldehyde in the approximate wherein R1 and R2 represent the same or diiferent radicalsselected from the group which consists of hydrogen and alkyl radicals which comprises reacting a hydantoin having the formula R1 and R2 representing the above-identified radicals, and in which the total number of carbon atoms in R1 and R2 does not exceed 5, with formaldehyde in an aqueous reaction mixture containing, atthe initiation of the reaction, a hydantoin. and formaldehyde in the approximate proportion of one mole of formaldehyde for each two moles of-thehydantoin, water in an amount between'l5r% and 35% by weight of thereaction mixture, a metallic chloride taken from the group consisting of zinc chloride and cadmium chloride,

and sufilcient hydrogen chloride to substantially saturate the reaction mixture.

4. A process for the production of N,N methylene bis-ldimethyl hydantoin which comprises reacting 5,5 dimethyl hydantoin with formaldehyde--.in an aqueous reaction mixture containing, ati'the initiation ofthe reaction, the hydantoin and formaldehyde in the approximate proportion of one .-'mole of formaldehyde for each two moles of said hydantoin, water in an amount between 15% and 35%, and hydrogen chloride between and 9%, by weight of the reaction mixture, and a metallic chloride taken from the group consisting of zinc chloride and cadmium chloride.

5. A process for the production of N,N methylene bis-methyl, ethyl hydantoin which comprises reacting fi-methyl, 5-ethy1 hydantoin with formaldehyde in an aqueous reaction mixture containing, at the initiation of the reaction, the hydantoin and formaldehyde in the approximate proportion of one mole formaldehyde for each two moles of said hydantoin, water in an amount between 15% and 35%, and hydrogen chloride between 9% and 14%, by weight of the reaction mixture, and a metallic chloride taken from the group consisting of zinc chloride and cadmium chloride.

6. A process for the production of N,N' methylene bis-methyl, isobutyl hydantoin which comprises reacting 5-methy1, 5-isobuty1 hydantoin with formaldehyde in an aqueous reaction mix- Number ture containing, at the initiation of the reaction, the hydantoin and formaldehyde in the approximate proportion of one mole formaldehyde for each two moles of said hydantoin, water in an amount between 15% and and hydrogen chloride between 16% and 19%, by weight of the reaction mixture, and a metallic chloride taken from the group consisting of zinc chloride and cadmium chloride.

7. As a new chemical compound N,N' methylene bis-5-methyl, 5-isobutyl hydantoin,

JOSEPH FREDERIC WALKER.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Jacobson .Apr. 25, 1939 Graenacher Dec. 17, 1940 OTHER REFERENCES Annalen, vol. 365, pages 38-49. 

